The ultimate goal of the proposed research project is to advance our understanding of esophageal cancer and the impact of cancer control interventions in order to diminish the burden of this disease. We will accomplish this goal through a collaborative and comparative modeling project. The incidence of esophageal adenocarcinoma (EAC) has been rising at an alarming rate over the past three decades. Although the absolute number of EAC cases per year remains too low to screen the general population, targeted screening may be appropriate. Heartburn, the primary symptom of gastroesophageal reflux disease (GERD), affects 60 million Americans and can lead to Barrett's esophagus (BE), a premalignant condition associated with the greatest risk (30-125x) of developing EAC. Because of the significant number of individuals affected with GERD and BE, the management of these patients has become a public health issue. However, an accepted screening or surveillance program for EAC has not been proposed. The goal of National Cancer Institute's (NCI) Cancer Intervention and Surveillance Modeling Network (CISNET), and a broader theme for our research proposal, is to bring together different simulation models, embracing differences in model structure to improve the overall understanding of a cancer's natural history and to improve model projections. Our application is in response to CISNET's recent expansion to include esophageal cancer as one of the targeted cancers within its network. As a new cancer group, we have the distinctive opportunity to perform groundbreaking analyses and to provide the crucial evidence synthesis that are urgently needed and novel. Our innovative collaboration will perform comparative modeling that focuses on, but is not limited to, determining the effectiveness of clinically relevant issues in esophageal cancer, multiscale modeling and incorporation of biomarkers, and the creation and dissemination of an interactive policy level decision tool. The investigators and the institutions assembled for this project have expertise in all facets of simulation disease modeling, clinical aspects of esophageal cancer, and a proven history of research and collaborations, providing assurance that the project's goals will be achieved in this rich environment. The research will address the overarching goals of increasing our understanding of the natural history of esophageal cancer and determining the impact and of potential cancer control interventions with the ultimate goal of ameliorating cancer morbidity.